Ultrasound-Mediated Destruction of P-Selectin-Targeted and Cannabinoid Type 2 Receptor Agonist-Loading Microbubbles Ameliorates Skeletal Muscle Ischemia-Reperfusion Injury in Rat

Abstract

Current study aims to explore the ameliorative effects of ultrasound in combination with P-selectin-targeted/AM1241-loaded microbubbles (AM1241 MBs) in rats with skeletal muscle ischemia/reperfusion (I/R) injury. AM1241 MB was prepared via rotary evaporation and mechanical shaking. Histological lesions and cellular apoptosis in skeletal muscle were detected by H&E staining and TUNEL staining, respectively. Changes in antioxidant capacity and inflammatory response in skeletal muscle tissue were analyzed by ELISA method. Changes of Nfr2/HO-1 pathway-related proteins were measured via the western blot. As a result, ultrasound-mediated destruction of AM1241 MBs significantly improved the degree of damage and edema in skeletal muscle tissue of rats with I/R injury. Inflammatory response and cellular apoptosis in skeletal muscle tissue were also significantly improved, while the antioxidant capacity was significantly enhanced. Western blot analysis exhibited that ultrasound in combination with AM1241 MBs treatment activated the Nrf2/HO-1 pathway. Nevertheless, selective knockdown of Nrf2 significantly reversed the beneficial effects of ultrasound combined with AM1241 MBs treatment on I/R injuries of the skeletal muscle. Ultrasound-mediated disruption of AM1241 MBs could effectively ameliorate the I/R injuries of skeletal muscle tissues in rats via activating the Nrf2/HO-1 pathway.